Effect of systemic administration of d-serine on the levels of d- and l-serine in several brain areas and periphery of rat.

摘要

To obtain further insight into the distribution and metabolism of exogenous d-serine, we have investigated the effect of the intraperitoneal administration of d-serine (10 mmol/kg) on the concentrations of d- and l-serine in several brain areas and periphery of infant and adult rats. The administration produced a significant augmentation of the d-serine levels not only in the cortex but also in the hippocampus, striatum, cerebellum and periphery. The rapid decline in the enhanced d-serine levels was observed in the periphery and cerebellum, whereas the injection caused a prolonged elevation of the d-serine levels in the cortex and hippocampus. The application caused a slight increase in the l-serine levels in several brain areas and periphery 3 or 6 h after the injection, whereas a significant decrease in the l-serine concentration was observed in the periphery, diencephalon and cerebellum 3 or 7 days after the injection. Because a structural abnormality and N-methyl-d-aspartate (NMDA) receptor hypofunction has been demonstrated in the cortex and hippocampus of schizophrenic subjects, d-serine treatment may offer a new therapeutic approach to diseases related to the hypofunction of NMDA receptors such as schizophrenia.